Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 1 Supplemental Material Chinese Stroke Association Guidelines for Clinical Management of Cerebrovascular Disorders Executive Summary and 2019 Update of Clinical Management of Ischemic Cerebrovascular Diseases Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 2 Section 1 Definitions associated with ischemic cerebrovascular diseases. The definitions of ischemic cerebrovascular disease are shown in Table 1. Section 2 Emergency assessment and diagnosis of ischemic stroke patients Please refer to Figure 1 for details of the management process for ischemic stroke patients in the acute phase. I. First assessment of emergency (I) Medical history collection Acute ischemic stroke (AIS) patients suffer from acute onset. It is very important to inquire about the time of occurrence of symptoms, onset characteristics and progress, including symptom persistence, fluctuations and relief. If the disease starts onset during sleep, the time when the patient's last normal performance should be recorded. These patients may also get sick shortly before waking up, and the onset time is uncertain, but clinically the final normal time should still be calculated as the last normal time [1-2]. Using MRI to screen wake-up stroke patients who are not suitable for thrombectomy, intravenous thrombolysis helps patients get good prognosis [3]. Before the occurrence of current symptoms, some patients will have similar TIA symptoms that can be relieved automatically. The time window for thrombolytic therapy is calculated based on the occurrence time of current symptoms. The inquiry about whether there are causes related to haemorrhagic stroke before the occurrence of symptoms, such as emotional excitement, intense exercise, sudden change of body position, excessive blood pressure reduction, as well as whether there is a history of Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 3 stroke or similar stroke-like diseases (such as epilepsy and hypoglycaemia attacks), has certain significance for diagnosis. Other medical history should include the presence or absence of atherosclerosis risk factors (such as hypertension, diabetes, and hyperlipidaemia) and heart disease risk factors (such as atrial fibrillation), drug abuse, migraine, infection, trauma, surgery and pregnancy history, and attention should be paid to the patient's recent medication, especially the presence or absence of anticoagulant drugs. For patients with consciousness disorder, doctors can ask their family members or witnesses about the disease. (II) Physical examination After emergency doctors and stroke team doctors evaluate the airway and respiratory and circulatory functions individually or jointly, they will immediately carry out general physical examination, including auscultation of large cervical vessels and heart. (III) Auxiliary examination (such as blood glucose, electrocardiogram, troponin, chest radiography) Timely imaging examination is very important for quick assessment and diagnosis of patients with possible ischemic stroke. All patients should first select urgent cranial CT examination to exclude cerebral haemorrhage, and MRI may be chosen if conditions permit, but should not delay thrombolysis therapy. For patients suspected of macrovascular occlusion, MRA or CTA should be performed as soon as possible (at the same time of thrombolysis) to determine whether intravascular treatment Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 4 conditions are available. For the process of skull imagological examination for patients suspected of ischemic stroke after entering the emergency department, see Supplemental Table 1. For all suspected stroke patients, routine laboratory examination should be carried out immediately upon arrival at the emergency department, including blood glucose, renal function, electrolyte, blood routine including platelet count, coagulation function including international standardized ratio (INR), myocardial ischemia markers, and bedside electrocardiogram examination should be performed. Because time is of the utmost importance, thrombolytic therapy should not be delayed due to waiting for the above laboratory results, unless the patient has oral anticoagulants or obvious history of coagulation. Retrospective analysis of patients receiving intravenous thrombolysis has found that the probability of unexpected coagulation disorders and thrombocytopenia is very low [4-5].For the vast majority of patients, blood glucose test results must be acquired before thrombolytic therapy [6]. Some laboratory tests can be selected for specific patients, toxicological screening can be performed for suspected drug abuse, chest radiography can be performed for suspected aortic dissection, electroencephalogram can be performed for suspected epilepsy, lumbar puncture can be performed for suspected intracranial infection or subarachnoid haemorrhage, blood gas examination can be performed for hypoxia, and pregnancy tests can be performed for women of childbearing age. For intravenous thrombolysis or mechanical thrombectomy, the earlier treatment is Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 5 started, the greater the benefit. Many studies abroad suggest that the average or median door-to-imaging time under different hospital configurations is less than 20min [7-10].However, a large-scale registration study in China in 2011 showed that the average door-to-needle time (DNT) in China was 116min, and the average imaging- to-needle time (INT) was 90min. Therefore, based on China's national conditions and actual clinical practice, skull imagological examination should be completed within 30min for patients suspected of ischemic stroke [11]. Recommendations [1] It is recommended that patients suspected of having an ischemic stroke should complete finish brain imaging within 30 minutes of arrival at the emergency department (Class I, Level of Evidence B). [2] Emergency assessment of blood glucose, renal function, electrolytes, complete blood count (including platelet count), blood coagulation (including INR), cardiac injury markers, and a bedside 12-lead ECG is recommended, but should not delay the initiation of IV rt-PA. For most patients, only the assessment of blood glucose must precede the initiation of IV rt-PA (Class I, Level of Evidence B). (IV) Definitions of penumbra Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 6 The hypoperfusion brain tissue is divided into three parts according to function and prognosis. The centre is the irreversible infarction core, and the outermost periphery is the hypoperfusion area with intact function. The area between them is the ischemic penumbra. The brain tissue in the penumbra is at risk of irreversible ischemic damage, but this part of brain tissue can be saved if blood perfusion is restored in time. Therefore, ischemic penumbra is currently an important therapeutic target for AIS [12]. The early studies mainly explored the best time window to save the penumbra [13-14]， but the general and narrow time window will cause many potentially beneficial patients to have poor prognosis due to failure to receive reperfusion therapy. With the development of multi-mode imaging, the penumbra can be accurately identified by judging whether the infarct core matches its peripheral hypoperfusion areas, which prolongs the treatment time window and has important clinical guiding value. Researchers further set a target mismatch (TMM) by comparing the relationship between different mismatch degrees and prognosis, which means that more ischemic penumbra can be saved under a specific mismatch threshold and the prognosis is better after reperfusion therapy [15]. Common imaging strategies include diffusion- perfusion imaging mismatch, CTP, clinical imaging mismatch and diffusion-flair mismatch. Other technologies such as DWI-SWI mismatch, ASL-PWI mismatch, APTW and MR OMI have been reported, but have not been applied to large-scale clinical trials [16-19]. Liu L, et al. Stroke Vasc Neurol 2020; 5:e000378. doi: 10.1136/svn-2020-000378 Supplementary material Stroke Vasc Neurol Supplemental Material Liu Page 7 In many large-scale clinical studies, for intravenous thrombolysis or intravascular therapy, such as DEFUSE, DEFUSE2, EPITHET, DEDAS, DAWN, and DEFUSE3, the most widely used and mature imaging strategy is diffusion-perfusion imaging mismatch (DWI-PWI mismatch) [15, 20-22]. It uses the mismatch between DWI infarction core area and PWI hypoperfusion area to identify ischemic penumbra. At present, the generally accepted set threshold is: the area with Tmax > 6s on PWI is set as the hypoperfusion area, the area with ADC < 600×10-6mm2/s on DWI is set as the infarction core area, and the target mismatch is defined as the area with infarction core area < 70ml, ischemic penumbra > 15ml, and the area with the ratio of total hypoperfusion area to ischemic core area being > 1.8 [15].At present, required data can be directly obtained by using software such as Rapid. Although the DWI-PWI mismatch